Exclusive KRAS mutation in microsatellite-unstable human colorectal carcinomas with sequence alterations in the DNA

Related Experiment Video

Updated: Jul 2, 2026

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
06:01

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer

Published on: July 6, 2017

Yan Zhao1, Kaname Miyashita, Takayuki Ando

  • 1Institute for Clinical Research, National Kyushu Cancer Center, 3-1-1, Notame, Fukuoka 811-1395, Japan.

Gene
|August 12, 2008
PubMed

Insights

Microsatellite instability (MSI) indicates DNA mismatch repair (MMR) defects. KRAS mutations are frequent in MMR-deficient colorectal tumors, particularly those with MLH1 alterations, challenging previous assumptions about sporadic cancers.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Microsatellite instability (MSI) is a hallmark of defective DNA mismatch repair (MMR).
  • MMR defects increase genomic instability, yet base substitutions in key genes are rare in MSI-positive tumors.
  • Colorectal tumors with MSI exhibit heterogeneity, with KRAS mutations noted in hereditary settings.

Purpose of the Study:

  • To investigate the frequency and context of KRAS gene mutations in human colorectal carcinomas with determined MSI status.
  • To explore the relationship between KRAS mutations, MSI status, and specific DNA mismatch repair gene alterations.

Main Methods:

  • Sequencing of the KRAS gene in 76 human colorectal carcinomas.
  • Determination of MSI status for all tumor samples.
  • Analysis of sequence alterations in MMR genes, specifically MLH1.

Main Results:

  • KRAS mutations were identified in 22 out of 76 (28.9%) colorectal tumors.
  • All KRAS-mutant, MSI-high (MSI-H) tumors exhibited alterations in the MLH1 gene.
  • KRAS mutations predominantly occurred in MMR gene-mutant MSI-H tumors, including some sporadic cases.

Conclusions:

  • KRAS mutations are significantly associated with MMR gene defects, particularly MLH1 mutations, in MSI-H colorectal tumors.
  • The findings suggest a complex interplay between MMR deficiency, KRAS mutations, and the mutator phenotype in colorectal carcinogenesis.
  • This challenges the prevailing view and highlights the importance of considering MMR gene status when evaluating KRAS mutations in colorectal cancer.

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